Title

Author

Date of Award

May 2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Advisor(s)

Eleanor Maine

Keywords

C. elegans, germline, H3K9me2, small RNA

Subject Categories

Life Sciences

Abstract

Heterochromatin assembly on repetitive sequences has been proposed to maintain genome integrity in different species. Histone H3 lysine 9 dimethylation (H3K9me2) has been shown to play an important role in mediating the formation of heterochromatin. In our lab, we use Caenorhabditis elegans as a model system to study the biological significance of the enrichment of H3K9me2 on repetitive elements and unpaired chromatin. Research of several other labs implicated that distribution of H3K9me2 on repetitive sequences limits transposon transcription and mutation occurrence near repetitive sequences. Additionally, our lab has reported that CSR-1 small RNA pathway (CSR-1, EKL-1, EGO-1 and DRH-3) regulates the deposition of H3K9me2 on unpaired chromatin during meiotic prophase.

In this study, I identified a putative DNA annealing helicase, SMRC-1, that associates with the H3K9me2 methyltransferase MET-2 and a modified form of EKL-1. The majority of this thesis focuses on understanding the interaction between MET-2 and SMRC-1. Characterization of smrc-1 mutants revealed that SMRC-1 is important for resolving replication stress. Thus the association between SMRC-1 and MET-2 might suggest H3K9me2 functions as an epigenetic regulator of double strand break formations genome wide. Additionally, I found that a modified form of EKL-1 might interact with SMRC-1. Based on these findings, I propose a model whereby SMRC-1 bridges the CSR-1 small RNA pathway with H3K9me2.